High-priced Genzyme drug is OK'd
1st remedy for rare Pompe disease
The drug, Myozyme, treats an incurable disease that causes muscle wasting in adults and fatal heart and lung failure in infants. It is currently known to affect only about 1,000 people.
''This is a special day for people across the Pompe community and at Genzyme," said Henri Termeer, the Cambridge company's chief executive.
By developing life-saving treatments for extremely rare illnesses, Genzyme has become the largest drug company in Massachusetts and one of the biggest biotechnology companies in the world. It has also emerged as a target for critics who say the healthcare system can't afford a growing stream of such high-priced drugs.
Myozyme joins the company's first two drugs for similarly rare genetic disorders, Cerezyme and Fabrazyme, which together treat just over 6,000 patients and last year made Genzyme over $1 billion. Myozyme could generate more than $100 million annually by 2010, according to analysts.
''We've been waiting for this for a long time," said Marylyn House of San Antonio, secretary of the Acid Maltase Deficiency Association, a Pompe patients group.
House's organization, which has spent years backing Pompe research and urging the government to approve Myozyme, is now helping patients figure out how their insurance coverage will handle a drug that can quickly exceed the lifetime maximum payouts of many policies.
''We're glad that we have a treatment," said House. ''It brings us new problems, though."
The development of Myozyme, which has cost Genzyme an estimated $500 million since 1998, illustrates the technical and medical challenges that have made biopharmaceuticals one of the most cash-intensive industries in the country.
It is also an extreme case study of the economics of the modern drug industry, which is shifting toward medicines designed to treat narrower segments of the patient population.
Myozyme supplies a missing protein in patients with Pompe disease. In its most severe form, the disease attacks infants, who develop severe heart and lung problems and die before they reach 18 months. In its milder adult form, patients become weak enough to require a wheelchair and ventilator and help with even simple physical tasks.
The drug's approval by the Food and Drug Administration marks a milestone in a scientific odyssey that began in 1932, when a young Dutch pathologist named J.C. Pompe described the mysterious death of an infant with an enlarged heart and unusual build-up of a sugar called glycogen in its muscles. Since then, researchers have slowly unlocked the disease's mysteries.
Pompe starts with a genetic mutation that prevents the body from making a crucial enzyme. Without it, a person cannot process glycogen to fuel muscles and tissues. Instead of being harmlessly digested inside cells, glycogen accumulates to lethal quantities in muscles, including the heart.
It was not until the late 1990s that a likely treatment began to emerge at a Dutch company that used an unusual technique: It genetically engineered rabbits to produce the enzyme in their milk. The company, Pharming, extracted the enzyme and gave it to seven patients in a clinical trial.
At the same time, researchers in Oklahoma, at Genzyme, and at Duke University were working on three other methods of producing the enzyme. Genzyme, which already made a similar therapy for a different disease, ended up licensing or buying all the competing Pompe programs. The rabbit-milk idea was discarded as impractical because it would take 70,000 rabbits to produce enough milk to treat the 3,000 to 5,000 patients Genzyme hoped to find, said company scientist Robert Mattaliano.
''I'm sure you don't want to hear about the intricacies of trying to milk rabbits," he said.
In a head-to-head laboratory trial that Genzyme scientists dubbed ''the mother of all experiments," they tested all four versions of the Pompe enzyme on mice that lacked it and found those receiving the Genzyme version were among the healthiest.
Once the company decided to turn the drug into a commercial product, however, it encountered a new problem: how to find patients. Pompe disease is so uncommon that few doctors had heard of it, and infants often died soon after they were diagnosed. Genzyme designed brochures, mailed cards, and even sent a decorative I.D. holder to doctors that included information on how to enroll patients.
''We sent out literally thousands and thousands of letters," said Tara O'Meara, who managed the clinical trial at Genzyme. ''but you just have to wait for the patients to be born."
It took a year to find 18 babies who qualified, an unusually small number for a clinical trial. Their families were scattered around the world. Two Palestinian families had to cross from Gaza to Israel for every treatment, spending hours at checkpoints with their sick daughters. One Turkish infant received the drug in England; another family from Peru moved to North Carolina to enroll, with Genzyme paying the family's housing costs.
The results were striking: All 18 babies on Myozyme survived to 18 months, although three were on ventilators. By comparison, medical records showed that only one in 50 untreated babies with the disease typically survived to that age. (The children, now toddlers, have continued to receive the drug, and 16 are still alive.) Yesterday's approval was based on results of that study, as well as other data Genzyme has not released.
The FDA said Myozyme can be prescribed not only to infants but to any patient diagnosed with Pompe disease. The drug also will include a ''black-box" warning detailing possible reactions, from a mild rash to anaphylactic shock, which are risks commonly associated with biologically produced drugs. The company is continuing tests to document Myozyme's effects on older patients.
Nearly 300 patients are already on the drug, most of them under programs that allow access to experimental drugs for humanitarian reasons. In two weeks, Genzyme expects to roll out the drug commercially and start sending bills to those patients for future treatment, shifting the focus from regulators to insurers. Along with the drug, Genzyme is simultaneously releasing a genetic test that should help doctors diagnose more cases.
Although Genzyme has not yet set a price for Myozyme, the company says it will cost as much as its drugs for other enzyme deficiencies. Under a 1983 law called the Orphan Drug Act, which rewards companies for pursuing treatments for rare diseases, Genzyme is allowed to sell Myozyme in the United States without competition for seven years, effectively setting its own price. Such drugs can cost hundreds of thousands of dollars a year, depending on how strong a dose the patient needs.
Genzyme provides counselors to patients having trouble convincing insurance companies to pay for treatments, and has already been in discussions with insurers about covering Myozyme.
''This is a sensational price point relative to what most other drugs cost," said David Meeker, president of the Genzyme division that makes Myozyme.
Meeker said Genzyme has succeeded in winning coverage for its previous enzyme drugs partly by explaining that such prescriptions are so rare that they have a relatively modest impact on insurers overall.
Tiffany House, Marylyn House's daughter, was one of the first patients to be tested with the rabbit-milk version of the enzyme. She was diagnosed with Pompe disease at age 11, lost the ability to walk, and was home-schooled in a wheelchair.
Since she started with the original trial in 1999, she said, her disease has stopped progressing, and she is slowly regaining strength. Although still in a wheelchair, she was able to enroll in college and is now studying for a master's degree in English.
''They told my mother that I wouldn't be alive by 20," said House, who was diagnosed before any treatment for the disease existed.
''Yes, it's worth the cost," she said, ''but how do I pay that cost? This is something I'm going to have to find a way to pay for the rest of my life, and I'm only 23, so that's a pretty long time."
Stephen Heuser can be reached at sheuser@globe.com. 
